Dengue viruses (DENV) are human pathogens with a significant threat to world health. These viruses are estimated to cause several hundred thousand cases of dengue fever, dengue hemorrhagic fever and dengue shock syndrome annually. There are four closely related serotypes of dengue viruses, DENV-1, DENV-2, DENV-3 and DENV-4, of the genus Flavivirus. The four viruses are spread from human to human through the bite of Aedes aegypti, a highly urbanized mosquito species that has successfully resisted all attempts at eradication and control. Vaccination is considered to be the only efficient method of control of dengue. To this end, several tetravalent dengue candidate vaccines are in late stages of development.
A first infection with one Dengue virus serotype induces a life-long protective immunity to the homologous serotype. However, there is no cross-protection against infection by a different serotype. Indeed, pre-existing immunity against one serotype is associated with increased risk for dengue infection and dengue hemorrhagic fever caused by a different serotype due to antibody-dependent enhancement (ADE) of infection. In ADE, antibodies raised by prior dengue infection or passively transferred from mother form infectious immune complexes that attach to Fc-receptor-bearing cells in the mononuclear phagocyte lineage resulting in efficient infection.
Accordingly, there is a need for materials and methods for preventing dengue virus infection without increasing the risk of antibody-dependent enhancement of infection.